This invention relates to certain substituted fused heterocyclic compounds which are useful as herbicides and their agriculturally suitable compositions as well as methods for their use as general or selective preemergent or postemergent herbicides or as plant growth regulants.
New compounds effective for controlling the growth of undesired vegetation are in constant demand. In the most common situation, such compounds are sought to selectively control the growth of weeds in useful crops such as cotton, rice, corn, wheat and soybeans, to name a few. Unchecked weed growth in such crops can cause significant losses, reducing profit to the farmer and increasing costs to the consumer. In other situations, herbicides are desired which will control all plant growth. Examples of areas in which complete control of all vegetation is desired are areas around railroad tracks, storage tanks and industrial storage areas. There are many products commercially available for these purposes, but the search continues for products which are more effective, less costly and environmentally safe.
U.S. Pat. No. 5,032,165 discloses herbicidal compounds of the formula 
The invention comprises novel compounds of Formula I, agriculturally suitable compositions containing them, and their method-of-use as preemergent and/or postemergent herbicides and/or plant growth regulants 
wherein
Q is 
G1 is CR1 or N;
G2 is CR4 or N;
A is C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 alkenyl, C2-C4 alkynyl, OR10, SR10 or halogen;
B is C1-C4 alkyl, C1-C4 haloalkyl, C3-C4 alkenyl or C3-C4 alkynyl;
A and B can be taken together as Xxe2x80x94Yxe2x80x94Z to form a fused ring such that X is connected to nitrogen and Z is connected to carbon;
X is CHR2, CH2CH2 or CR2xe2x95x90CR3;
Y is CHR5, CR5xe2x95x90CR6, CHR5CHR6, NR7, O or S(O)n;
Z is CHR8, CH2CH2, CR8xe2x95x90CR9, NR7, O or S(O)n;
n is O, 1 or 2;
R1 and R4 are independently halogen or CN;
R2, R3, R5, R6, R8 and R9 are independently H, halogen, C1-C4 alkyl or C1-C4 haloalkyl;
R7 is H, C1-C4 alkyl or C1-C4 haloalkyl;
W is O or S;
R10 is C1-C4 alkyl or C1-C4 haloalkyl;
R11 is halogen;
R12 is H, C1-C8 alkyl, C1-C8,haloalkyl, halogen, OH, OR17, SH, S(O)nR17, COR17, CO2R17, C(O)SR17, C(O)NR19R20, CHO, CR19xe2x95x90NOR26, CHxe2x95x90CR27CO2R17, CH2CHR27CO2R17, CO2Nxe2x95x90CR21R22, NO2, CN, NHSO2R23, NHSO2NHR23, NR17R28, NH2 or phenyl optionally substituted with R29;
R13 is C1-C2 alkyl, C1-C2 haloalkyl, OCH3, SCH3, OCHF2, halogen, CN or NO2;
R14 is H, C1-C3 alkyl or halogen;
R15 is H, C1-C3 alkyl, halogen, C1-C3 haloalkyl, cyclopropyl, vinyl, C2 alkynyl, CN, C(O)R28, CO2R28, C(O)NR28R30, CR24R25CN, CR24R25C(O)R28, CR24R25CO2R28, CR24R25C(O)NR28R30, CHR24OH, CHR24OC(O)R28 or OCHR24OC(O)NR28R30;
when Q is Q-2 or Q-6, R14 and R15 together with the carbon to which they are attached can be Cxe2x95x90O;
R16 is H, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkoxyalkyl, C3-C6 alkenyl, C3-C6 alkynyl or 
R17 is C1-C8 alkyl; C3-C8 cycloalkyl; C3-C8 alkenyl; C3-C8 alkynyl; C1-C8 haloalkyl; C2-C8 alkoxyalkyl; C2-C8 alkylthioalkyl; C2-C8 alkylsulfinylalkyl; C2-C8 alkylsulfonylalkyl, C4-C8 alkoxyalkoxyalkyl; C4-C8 cycloalkylalkyl; C4-C8 alkenoxyalkyl; C4-C8 alkynoxyalkyl; C6-C8 cycloalkoxyalkyl; C4-C8 alkenyloxyalkyl; C4-C8 alkynyloxyalkyl; C3-C8 haloalkoxyalkyl; C4-C8 haloalkenoxyalkyl; C4-C8 haloalkynoxyalkyl; C6-C8 cycloalkylthioalkyl; C4-C8 alkenylthioalkyl; C4-C8 alkynylthioalkyl; C1-C4 alkyl substituted with phenoxy or benzyloxy, each ring optionally substituted with halogen, C1-C3 alkyl or C1-C3 haloalkyl; C4-C8 trialkylsilylalkyl; C3-C8 cyanoalkyl; C3-C8 halocycloalkyl; C3-C8 haloalkenyl; C5-C8 alkoxyalkenyl; C5-C8 haloalkoxyalkenyl; C5-C8 alkylthioalkenyl; C3-C8 haloalkynyl; C5-C8 alkoxyalkynyl; C5-C8 haloalkoxyalkynyl; C5-C8 alkylthioalkynyl; C2-C8 alkyl carbonyl; benzyl optionally substituted with halogen, C1-C3 alkyl or C1-C3 haloalkyl; CHR24COR18; CHR24P(O) (OR18)2; CHR24P(S) (OR18)2; CHR24C(O)NR19R20; CHR24C(O)NH2; CHR24CO2R18;
CO2R18; SO2R18; phenyl optionally substituted with R29; 
R18 is C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 alkenyl or C3-C6 alkynyl;
R19 and R21 are independently H or C1-C4 alkyl;
R20 and R22 are independently C1-C4 alkyl or phenyl optionally substituted with halogen, C1-C3 alkyl or C1-C3 haloalkyl;
R19 and R20 may be taken together as xe2x80x94(CH2)5xe2x80x94, xe2x80x94(CH2)4xe2x80x94 or xe2x80x94CH2CH2OCH2CH2xe2x80x94, each ring optionally substituted with C1-C3 alkyl, phenyl or benzyl;
R21 and R22 may be taken together with the carbon to which they are attached to form C3-C8 cycloalkyl;
R23 is C1-C4 alkyl or C1-C4 haloalkyl;
R24 and R25 are independently H or C1-C4 alkyl;
R26 is H, C1-C6 alkyl, C3-C6 alkenyl or C3-C6 alkynyl;
R27 is H, C1-C4 alkyl or halogen;
R28 and R30 are independently H or C1-C4 alkyl; and
R29 is C1-C2 alkyl, C1-C2 haloalkyl, OCH3, SCH3, OCHF2, halogen, CN or NO2;
and their corresponding N-oxides and agriculturally suitable salts provided that
1) the sum of X, Y, and Z is no greater than 5 atoms in length and only one of Y and Z can be other than a carbon containing link;
2) when A and B are other than taken together as Xxe2x80x94Yxe2x80x94Z then G1 is N and G2 is CR4;
3) when R12 is CO2R17, C(O)SR17, CHxe2x95x90CR27CO2R17 or CH2CHR27CO2R17 then R17 is other than C1 haloalkyl and when R17 is CHR24CO2R18 or CO2R18 then R18 is other than C1 haloalkyl; and
4) when G1 is N then G2 is CR4, and when G2 is N then G1 is CR1.
In the above definitions, the term xe2x80x9calkylxe2x80x9d, used either alone or in compound words such as xe2x80x9calkylthioxe2x80x9d or xe2x80x9chaloalkylxe2x80x9d, includes straight chain or branched alkyl, e.g., methyl, ethyl, n-propyl, isopropyl or the different butyl isomers. Alkoxy includes methoxy, ethoxy, n-propyloxy, isopropyloxy, the different butoxy isomers, etc. Alkenyl and alkynyl include straight chain or branched alkenes and alkynes, e.g., 1-propenyl, 2-propenyl, 3-propenyl and the different butenyl isomers. Cycloalkyl includes cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc. The term xe2x80x9chalogenxe2x80x9d, either alone or in compound words such as xe2x80x9chaloalkylxe2x80x9d, means fluorine, chlorine, bromine or iodine. Further, when used in compound words such as xe2x80x9chaloalkylxe2x80x9d said alkyl may be partially or fully substituted with halogen atoms, which may be the same or different. Examples of haloalkyl include CH2CH2F, CF2CF3 and CH2CHFCl.
The compounds of the invention preferred for reasons including ease of synthesis and/or greater herbicidal efficacy are:
1) Compounds of Formula I wherein R2, R3, R5, R6, R8 and R9 are independently H, F, CH3 or CF3.
2) Compounds of Preferred 1 wherein
R12 is H, OR17, SR17 or CO2R17;
R13 is halogen or CN.
3) Compounds of Preferred 2 wherein
Q is Q-1, Q-2, Q-4 or Q-5;
A and B are taken together as Xxe2x80x94Yxe2x80x94Z;
X is CHR2;
Y is CHR5 or CHR5CHR6;
Z is CHR8;
R2, R3, R5, R6, R8 and R9 are independently H or F;
R17 is C1-C4 alkyl, C3-C4 alkenyl, C3-C4 
alkynyl, C2-C4 alkoxyalkyl, C1-C4 haloalkyl,
C3-C4 haloalkenyl or C3-C4 haloalkynyl.
4) Compounds of Formula I wherein G1 is N.
5) Compounds of Formula I wherein G2 is N.
The compounds of the invention specifically preferred for reasons of greatest ease of synthesis and/or greatest herbicidal efficacy are the compounds of Preferred 3 which are:
3-bromo-2-[4-chloro-2-fluoro-5-(2-propynyloxy)-phenyl]-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine;
3-chloro-2-[4-chloro-2-fluoro-5-(2-propynyloxy)-5,6,7,8-tetrahydoimidazo[1,2-a]pyridine; and
6-(3-chloro-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-2-yl)-7-fluoro-4-(1-methyl-2-propynyl)-2H-1,4-benzoxazin-3(4H)-one.
Another embodiment of the invention is an agriculturally suitable composition for controlling the growth of undesired vegetation comprising an effective amount of a compound of Formula I with the substituents as defined above.
A further embodiment of the invention is a method for controlling the growth of undesired vegetation which comprises applying to the locus to be protected an effective amount of a compound of Formula I with the substituents as defined above.
Compounds of Formula I may exist as one or more stereoisomers. The various stereoisomers include enantiomers, diastereomers and geometric isomers. One skilled in the art will appreciate that one stereoisomer may be the more active. One skilled in the art knows how to separate said enantiomers, diasteriomers and geometric isomers. Accordingly, the present invention comprises racemic mixtures, individual stereoisomers, and optically active mixtures.
Synthesis
By using one or more of the reactions and techniques described in Schemes 1-18 of this section as well as by following the specific procedures given in Examples 1-20, compounds of General Formula I can be prepared.
Compounds of Formula Ia, where Q, X, Y, and Z are defined as above, can be prepared by the method in Scheme 1. Reaction of an aminoheterocycle of Formula II with an alpha-bromo or chloroketone of Formula III in a solvent such as acetonitrile or methanol at room temperature or by heating followed by neutralization with a base such as saturated aqueous sodium bicarbonate affords compounds of Formula Ia. Aminoheterocycles of Formula II are known and can be commercially purchased in some cases.
Halogenation of compounds of Formula Ia with halogenating agents such as N-halosuccinimides or bromine affords compounds of Formula Ib (where R1 is halogen). Treatment of compounds of Formula Ia with Vilsmeier Reagent (phosphorous oxychloride, N,N-dimethylformamide) gives aldehyde adducts (of Formula Ib where R1 is a formyl group) which can be condensed with hydroxylamine hydrochloride to give oxime intermediates (Ib where R1 is Cxe2x95x90NOH) which in turn can be heated in phosphorous oxychloride to yield cyano substituted analogs of Formula Ic. 
The alpha-bromo and chloroketone of Formula III can be made by the methods summarized in Scheme 2. Carboxylic acids of Formula IV can be treated with thionyl chloride to give an acid chloride which in turn is allowed to react with Grignard reagent of Formula MeMgBr or MeMgCl or with methyl lithium to furnish ketone intermediates of Formula V. Lithiation of arylhalides of Formula VI followed by treatment with reagents of formula MeCOL (where L represents a leaving group such as halogen, dialkylamine, or alkoxide) gives ketones V as well. By the method of Beech [J. Chem. Soc. 1297 (1954)], ketones of Formula V can also be prepared from arylamines of Formula VII by diazotization followed by reaction of the generated diazonium salt with acetaldehyde oxime (MeCHxe2x95x90NOH) and hydrolysis. The starting materials IV, VI, and VII are known and can be commercially obtained in some cases. 
An alternative and more specific method for preparing tetrahydroimidazo[1,2-a]pyridine intermediates of Formula Id where R2, R5, R6, R8, and Q are defined as above (except when R16 or R17 on Q is an unsaturated group) is shown in Scheme 3. Heating 2-aminopyridines of Formula VIII with an alpha-bromo or chloroketone of Formula III followed by neutralization with saturated aqueous sodium bicarbonate gives imidazo[1,2-a]pyridines of Formula IX. Catalytic hydrogenation of imidazopyridines IX with a transition metal catalyst such as platinum oxide affords the tetrahydro analogs Id. Use of 2-aminothiazoles, 2-aminoxazoles, 2-aminopyrimidines, 2-aminopyridazines, and 2-aminopyrazines in place of the 2-aminopyridine starting materials in Scheme 3 and following this same method of synthesis also gives compounds of Formula Ia where X, Y, and Z are heteroatoms. 
Tetrahydroimidazo[1,2-a]pyridines of Formula Ib or Id where R16 or R17 on Q is methyl or benzyl can be deprotected with borontribromide to give dealkylated intermediates (where R16 and R17 are hydrogen) which on realkylation with alkenyl or alkynyl halides give compounds of Formula Ib or Id where R16 or R17 represents an alkenyl or alkynyl moiety.
Intermediate imidazo[1,2-a]pyridines of Formula IX can also be made by the route shown in Scheme 4. Condensing aminopyridines of Formula X with bromoacetic acid followed by heating the obtained condensation adducts with phosphorous oxybromide gives 2-bromoimidazo[1,2-a]pyridines of Formula XI. Palladium-catalyzed cross-couplings [using bis(triphenylphosphine)palladium(II) chloride or tetrakis(triphenylphosphine)palladium(0)] of these bromoimidazopyridines with boronic acids of formula QB(OH)2 in a solvent such as glyme in the presence of base such as aqueous sodium bicarbonate yields imidazo[1,2-a]pyridines of Formula IX. 
Dihydroimidazo[1,2-a]pyridines of Formula Ie and If can be synthesized by the chemistry shown in Scheme 5. Warming tetrahydroimidazopyridines of Formula Id with an excess of N-halosuccinimides (2.0-2.5 equivalents) in dimethylformamide at 60-100xc2x0 C. produces Ie and If. 
Scheme 6 illustrates the preparation of imidazoles of Formula Ig where R1 is halogen, and Q, A, and B are as previously defined. Amidines, isoureas, and isothioureas of Formula XII can be heated with alpha-bromo and chloroketones of Formula III, or with a corresponding alpha-hydroxyketone, in a solvent such as ethanol or dimethylformamide to give, after neutralization with a base such as aqueous saturated sodium bicarbonate, intermediates of Formula XIII. Alkylation of intermediates of Formula XIII with alkylating agents of Formula BL1 (where L1 is a leaving group) affords imidazoles of Formula XIV which on halogenation gives 5-haloimidazoles of Formula Ig where R1 is halogen. Halogenation of compounds of Formula XIV where A is hydrogen with an excess of the halogenating reagent produces imidazoles of Formula Ig where both A and R1 is halogen. 
An alternative method of preparing compounds of Formula XIV is shown in Scheme 7. Palladium-catalyzed cross-couplings [using for example bis(triphenylphosphine)palladium(II) chloride or tetrakis(triphenylphosphine)palladium(0)] of 4-bromoimidazoles of Formula XV with boronic acids of Formula QB(OH)2 in a solvent such as glyme in the presence of base such as aqueous sodium bicarbonate yields compounds of Formula XIV. Bromoimidazoles of Formula XV can be prepared by established methods. 
Salts (e.g., hydrochlorides and N-oxides) of I and II can be made by reaction of the free bases with an appropriate acid or oxidizing agent such as meta-chlorperoxybenzoic acid.
Scheme 8 describes how compounds of Formula I (where G2xe2x95x90N, G1xe2x95x90CR1 and A and B are Xxe2x80x94Yxe2x80x94Z) can be made by the reaction of sydnones of Formula XVI with appropriately substituted alkynes XVII. The reaction takes place at elevated temperatures generally between 80xc2x0 C. and 200xc2x0 C. The reaction may be performed in a variety of solvents with aromatic hydrocarbons such as xylenes being preferred. 
Scheme 9 describes how compounds of Formula I can be made by the reaction of sydnones with appropriately substituted alkenes XVIII. The initial product of the reaction is a dihydro aromatic compound. Often this is converted directly to the desired structure (Ih) in situ. It is also possible to include an oxidant such as chloranil or other mild oxidizing agent in the reaction mixture so as to make the aromatization process more facile (this has been shown with simpler sydnones: Huisgen et al.; Chem. Ber. 1968, 101, 829). The conditions for the reaction are as described above. The sydnones used in the above-mentioned processes can be made using procedures known in the art. (see S. D. Larsen and E. Martinborough, Tet. Lett. 1989, 4625) The chemistry of bicyclic sydnones has been reviewed (see Kevin Potts in xe2x80x9c1,3-Dipolar Cycloaddition Chemistryxe2x80x9d, Volume II, pages 50-57; A. Padwa editor, Wiley Interscience, New York, 1984). 
Scheme 10 describes an alternative synthesis of compounds of the invention by the photochemical cycloaddition of alkynyl substituted tetrazoles (XIX). The reaction can be performed in a variety of solvents, but is preferably carried out in inert solvents such as benzene or toluene. The reaction must be carried out in a vessel that allows the passage of light at wavelengths between 250 and 300 nm such as those made from quartz or vycor. The photolysis is preferably performed with a high pressure mercury arc lamp or other lamp which produces light above 250 nm. The reaction is carried out at room temperature or above. 
Scheme 11 describes how the tetrazoles XIX are made by alkylation of the free tetrazole XX with a halide or sulfonate in the presence of an acid acceptor or base. Many different bases such as alkali carbonates, hydroxides or hydrides are suitable. A variety of solvents can be used, but solvents of high polarity such as dimethylformamide or dimethyl acetamide are preferred. Tetrazoles XX can also be alkylated with alcohols XXI using the Mitsonobu reaction with a phosphine and a diazodicarboxylate. There are many different solvents and conditions that can be used. (See O. Mitsonobu, Synthesis, 1981, 1) Especially useful conditions for the instant invention include carrying out the reaction in tetrahydrofuran with diethyl azodicarboxylate and triphenylphosphine. Under these conditions the desired 3-alkynyl tetrazole (V) is produced predominantly. 
Scheme 12 describes how compounds of the instant invention (Ih or Ij, R1xe2x95x90H) can be converted to other compounds of the present invention (Ih or Ij, R1xe2x95x90Cl or Br) by reaction with halogenating agents. The reaction may be carried out with elemental halogens and also with N-halosuccinimides. The reaction with N-halosuccinimides gives particularly good results when conducted in dipolar aprotic solvents such as dimethylformamide. 
Scheme 13 shows how compounds of Formula Ih can also be prepared by coupling compounds of Formula Ih, Qxe2x95x90SnR3, with aryl halides or sulfonates (XXVII) in the presence of palladium catalysts such as those described in Scheme 7. For an example of this type of coupling with monocyclic pyrazoles, see Yamanaka et al., Heterocycles, 33, 813-818 (1992). Compounds of Formula Ih, Qxe2x95x90SnR3, can be made by sydnone cycloaddition as described in Scheme 8 using stannylated acetylenes. 
As shown in Scheme 14 some compounds of formula Ii where G2xe2x95x90N can be prepared by catalytic hydrogenation of compounds of Formula XXIII. The conditions are those disclosed in Scheme 3. Compounds of Formula XXIII can be prepared by cyclization of N-aminopicoline salts (XXI) with acid chlorides (XXII). The reaction is best performed in the presence of a base, preferably an amine base. Specifically preferred conditions are to run the reaction at elevated temperature (50-80xc2x0 C.) in the amine base, such as pyridine, as solvent (see Potts et al., J. Org. Chem., 33, 3767-3770 (1969). 
Scheme 15 describes how other compounds of the invention (Ij) can be obtained by the reaction of Munchnones (reactive mesoionic intermediates) with acetylenes (III). The Munchnones are prepared in the presence of the dipolarphile by dehydrating N-acyl-aminoacids (XXIV). The cycloaddition reaction occurs at elevated temperatures, generally between 50xc2x0 C. and 160xc2x0 C. Dehydrating agents such as acetic anhydride are very useful in this process. Other reagents and conditions for generating Munchnones have been described by Huisgen et al., Chem. Ber., 1970, 103, 2315. 
Scheme 16 describes how munchnones can also be made by the reaction of imides of structure (XXV) and a dehydrating agent in the presence of the alkene or alkyne. Many dehydrating reagents can be used. If the reagent used is acetic anhydride, it is convenient to use it as the solvent of the reaction. If a reagent such as a dicyclohexylcarbodiimide (DCC) is used, aromatic hydrocarbons such as benzene, toluene, or xylenes are preferred as solvents. The reaction is generally carried out at elevated temperature from 50xc2x0 C. to 180xc2x0 C. The chemistry of the bicyclic munchnones has been reviewed by Kevin Potts in xe2x80x9c1,3-Dipolar Cycloaddition Chemistryxe2x80x9d, Volume II, pages 41-49 (A. Padwa editor, Wiley Interscience, New York, 1984). 
The alkenes and alkynes (XVII and XVIII) are often commercially available. Scheme 7 describes how a generally useful method of synthesis is to couple aryl bromides and iodides (XXVII) with alkenes and alkynes in the presence of palladium catalysts. Appropriate catalysts and conditions are described in detail by Heck in xe2x80x9cPalladium Reagents in Organic Synthesesxe2x80x9d, Academic Press, New York, 1985. The aryl halides (XXVII) used for the instant invention are either commercially available or synthesized via diazotization of known arylamines (XXVI). Suitable conditions for diazotization of arylamines (XXVI) and their conversion to aryl halides (XXVII) can be found in Furniss et al, xe2x80x9cVogel""s Textbook of Practical Organic Chemistry, Fifth Editionxe2x80x9d, Longman Scientific and Technical, Essex, England, pages 922-946. There are many other known methods to incorporate iodine into aromatic molecules (see, Merkushev, Synthesis, 9213-937 (1988). 
Compounds of Formula Ik where R12xe2x95x90OH can serve as intermediates for the synthesis of compounds of Formula I containing many different R12 substituents. Scheme 18 shows some, but not all of the more useful transformations. In addition to well known alkylation and acylation chemistry, through the intermediacy of the triflate Il(R12xe2x95x90OSO2CF3) a wide variety of R12 substituents can be introduced. To form esters (Im) (R12xe2x95x90CO2R17)Il may be reacted with carbon monoxide and an alcohol in the presence of a suitable palladium catalyst (see Chem. Comm. 1987, 904-905). To form alkenes (In) the triflates (Il) may be reacted with an alkene in the presence of a palladium catalyst (see Heterocycles, 26, 355-358 (1987)). Ketones (Ip) may be formed by reaction of enol ethers under similar conditions (see J. Org. Chem., 57, 1481-1486 (1992)). Aryl groups (Iq) can be introduced by reaction of aryl boronic acids ArB(OH)2 with palladium catalysts (see Tetrahedron Lett., 32, 2273-2276 (1991) and references cited therein)). Alkyl groups (Ir) may be introduced by nickel or palladium catalyzed reaction with grignard reagents (see, J. Org. Chem., 57, 4066-4068 (1992) and references cited therein). 